BIOL 629: Host-Microbe Interactions
Supplementary Information (November 6, 2012)
Rational for adding the course:
This is a course within the Biology Department curriculum for graduate students that examines
the genetic and molecular processes that underlie symbiotic microbe-host associations from the
perspective of both partners. It is becoming apparent that these interactions have a significant
impact on human health and the environment. Therefore, it has become important for students to
develop an understanding of how these interactions are established and maintained, as well as
how they can be studied in the laboratory in order to develop a better understanding of factors
required for successful symbiosis. Because this is an area of active research, the course will be
updated each year and will remain relevant for many years to come. Students will read primary
literature and current review articles, and these readings will serve directly as discussion topics
during the class period. Students will be ask questions about research goals, methodologies, and
how they would carry out the next step of research. This proposed course covers an area of
biology not offered by the current curriculum, complements the existing molecular and genetics
offerings in the graduate curriculum, and will also be of interest to graduate students studying
evolution and ecology.
How the course serves students:
The study of host-microbe interactions is critical to an understanding of both human biology and
certain ecological processes. I anticipate that this course will be of interest to students in the
Biology Department’s MS programs (Biology, Biotechnology, and Biotechnology Certificate),
PhD programs (primarily the Molecular, Cellular and Organismal Biology and the Inter-campus
Biomedical Engineering and Biotechnology programs, but also Environmental Biology). This
proposed course covers an area of biology not offered by the current curriculum and
complements the existing molecular and genetics offerings in the graduate curriculum.
1
Detailed draft syllabus: (Note that this course was taught as a Special Topics BIOL 697 in Fall
2009.)
Course description and goals: This course will examine the genetic and molecular processes
that underlie symbiotic microbe-host associations from the perspective of both partners. Topics
will include the molecular genetics of model symbioses and the role of evolution and ecology in
shaping these interactions. Students will read primary literature and current review articles, and
these readings will serve as discussion topics during the class period.
Course Instructor: Katherine Gibson, Ph.D., Assistant Professor of Biology, University of
Massachusetts Boston.
Office: W-3-012. Phone: 617-287-6614. Email: katherine.gibson@umb.edu
Credits: 3 graduate credits
Class meetings: The course will meet for the duration of the Fall semester, two days a week,
Tuesday and Thursday, from 5 to 6:30 PM in the McCormick Biology conference room (M-1318).
Course website: http://boston.umassonline.net via UMass Online. This is a web-enhanced
course and students are required to attend lectures.
Target audience and prerequisites: This course is designed for Master’s and Ph.D. students in
the Molecular, Cellular and Organismal Biology (MCOB) track and is offered as an elective.
Knowledge of basic cell biology, genetics, and molecular biology is required (BIOL 372, or its
equivalent). Advanced Undergraduates are also eligible to take this course if they have already
completed BIOL 334 (Microbiology) and have the permission of the instructor.
Readings: A set of primary literature articles will be assigned for each class meeting and
supplemented with one or more current review articles for necessary background information on
each topic. The course syllabus, a full reading list, and a pdf of each article will be available on
the course website.
Course format and student evaluation: This course strongly emphasizes class discussion of the
assigned current literature article. Students will be asked to discuss the assigned reading in detail
during class. The course will also include two exams. Grading will be based on the following
components:
Class participation (40% of grade)
Midterm Exam (30% of grade)
Final Exam (30% of grade)
Academic honesty and misconduct: Academic dishonesty will not be tolerated and will be
dealt with very seriously. Students are expected to adhere to the Code of Student Conduct, which
can be found here: http://www.umb.edu/students/student_rights/code_conduct.html
Accommodations for students with disabilities: Students who qualify for accommodations due
2
to disabilities must submit the necessary documentation to the Ross Center for Disability
Services (Campus Center, UL-221; 617-287-7430). This documentation needs to be presented to
the Ross Center in a timely fashion. The Ross Center will assist students with obtaining the
appropriate accommodations for the course. More information, including information about
requesting accommodations (including important information such as deadlines that must be
adhered to for service requests), can be found here: http://www.rosscenter.umb.edu/
3
Preliminary Course Outline and Bibliography: (Readings are subject to change as they
become updated each year based on recent publications.)
Week 1. Legume–Rhizobium Signals: Flavonoids, NodD, and Host-Range
The nitrogen-fixing symbiosis between rhizobial bacteria and their legume hosts is one of the
best-characterized model systems in the field of host-microbe interactions. In particular, the
signal exchange between the two symbionts that is required to establish species-specificity in this
interaction has been studied in depth. We will begin by discussing the flavonoid chemical signal
produced by the plant host. We will examine how the plant signal was experimentally identified,
and how it is recognized by the bacterial symbiont.




Gibson (2008) Molecular determinants of a symbiotic chronic infection. Annu Rev Genet
42:413-41.
Zhang (2009) Flavones and flavonols play distinct critical roles during nodulation of
Medicago truncatula by Sinorhizobium meliloti. Plant J 57(1):171-83.
Schlaman (1992) Regulation of nodulation gene expression by NodD in rhizobia. J
Bacteriol 174(16):5177-82.
Horvath (1987) Host-specific regulation of nodulation genes in Rhizobium is mediated
by a plant-signal, interacting with the nodD gene product. EMBO J 6(4):841-8.
Week 2. Legume–Rhizobium Signals: Nod Factor
We will continue our discussion of the nitrogen-fixing symbiosis between rhizobial bacteria and
their legume hosts. We will shift our focus to a chemical signal, Nod Factor, produced by the
bacterial symbiont in response to host flavonoid. Nod Factor is absolutely required to establish
species-specificity in this interaction and allow bacterial infection of plant roots. We will
examine how the signal was experimentally identified, and how its precise chemical structure is
critical for the host to allow bacterial infection of its tissues.




Dénarié (1993) Lipo-oligosaccharide nodulation factors: a new class of signaling
molecules mediating recognition and morphogenesis. Cell 74(6):951-4.
Stougaard (2000) Regulators and regulation of legume root nodule development. Plant
Physiol 124(2):531-40.
Ehrhardt (1996) Calcium spiking in plant root hairs responding to Rhizobium nodulation
signals. Cell 85(5):673-81.
Ehrhardt (1992) Depolarization of alfalfa root hair membrane potential by Rhizobium
meliloti Nod factors. Science 256(5059):998-1000.
Week 3. Legume–Rhizobium Signals: Nod Factor Perception Pathway
We will continue our discussion of the nitrogen-fixing symbiosis between rhizobial bacteria and
their legume hosts. We will examine key host physiological responses to bacterial Nod Factor,
such as membrane depolarization. These plant responses have served as an important output for
identifying and characterizing host signal transduction pathway components required for
4
symbiont recognition and symbiosis development. This serves as an excellent model system for
establishing genetic epistasis within a signal transduction pathway.





Spaink (2004) Specific recognition of bacteria by plant LysM domain receptor kinases.
Trends Microbiol 12(5):201-4.
Catoira R (2000) Four genes of Medicago truncatula controlling components of a nod
factor transduction pathway. Plant Cell 12(9):1647-66.
Limpens (2003) LysM domain receptor kinases regulating rhizobial Nod factor-induced
infection. Science 302(5645):630-3.
Smit (2007) Medicago LYK3, an entry receptor in rhizobial nodulation factor signaling.
Plant Physiol 145(1):183-91.
Radutoiu (2007) LysM domains mediate lipochitin-oligosaccharide recognition and Nfr
genes extend the symbiotic host range. EMBO J 26(17):3923-35.
Week 4. Evolutionary Perspective on Mutualism
How does a host ensure that each bacterial symbiont is actively providing a benefit to its growth?
In our final discussion of the nitrogen-fixing symbiosis between rhizobial bacteria and their
legume hosts, we will discuss how mutualistic symbioses are maintained over evolutionary time.
In this system, the host continually measures bacterial productivity and generates sanctions
against less active symbionts, which serves as a selective pressure against the evolution of
cheaters within bacterial populations.



Denison (2004) Lifestyle alternatives for rhizobia: mutualism, parasitism, and forgoing
symbiosis. FEMS Microbiol Lett 15;237(2):187-93.
Kiers (2003) Host sanctions and the legume-rhizobium mutualism. Nature 425(6953):7881.
Heath (2009) Stabilizing mechanisms in a legume-rhizobium mutualism. Evolution
63(3):652-62.
Week 5. Squid-Vibrio Species Specificity
The symbiosis between light-producing bacteria and their aquatic squid host is another wellcharacterized model system in the field of host-microbe interactions. Characterization of this
symbiosis in particular has highlighted the striking similarities between how both beneficial
bacterial and harmful pathogens are recognized by the host. Similar bacterial signals are
monitored, but have a very different impact on the host depending on species-specificity. We
will discuss how species specificity is established in this beneficial symbiosis through host
production of both positive chemoattractants for the symbiont and negative toxins that block
non-symbiotic bacteria from access to the host tissues.


Nyholm (2004) The winnowing: establishing the squid-vibrio symbiosis. Nat Rev
Microbiol 2(8):632-42.
Nyholm (2003) Dominance of Vibrio fischeri in secreted mucus outside the light organ of
Euprymna scolopes: the first site of symbiont specificity. Appl Environ Microbiol
5

69(7):3932-7.
Davidson (2004) NO means 'yes' in the squid-vibrio symbiosis: nitric oxide (NO) during
the initial stages of a beneficial association. Cell Microbiol 6(12):1139-51.
Week 6. Squid-Vibrio Species Specificity
We will continue our discussion of the Squid and Vibrio symbiosis, and shift our attention from
the host factors towards the identification of bacterial factors that are required to establish
species specificity and productive host colonization.



Visick (2006) Vibrio fischeri and its host: it takes two to tango. Curr Opin Microbiol
9(6):632-8.
Yip (2006) The symbiosis regulator rscS controls the syp gene locus, biofilm formation
and symbiotic aggregation by Vibrio fischeri. Mol Microbiol 62(6):1586-600.
Mandel (2009) A single regulatory gene is sufficient to alter bacterial host range. Nature
458(7235):215-8.
Week 7. Microbial Remodeling of Host Tissues
In many beneficial symbiotic interactions, there is significant remodeling of host tissues in order
to successfully house the bacterial symbiont within a specific location and also limit its growth
so that it does not take over the host body and cause harm. We will discuss the types of signals
that bacteria produce in order to elicit host remodeling of tissues, for example the bacterial
lipopolysaccharide, which in harmful bacterial interactions with humans elicits an immune
response.


Montgomery (1994) Bacterial symbionts induce host organ morphogenesis during early
postembryonic development of the squid Euprymna scolopes. Development 120(7):171929.
Foster (2000) Vibrio fischeri lipopolysaccharide induces developmental apoptosis, but
not complete morphogenesis, of the Euprymna scolopes symbiotic light organ. Dev Biol
226(2):242-54.
Week 8. Midterm Exam
Week 9. Microbial Remodeling of Host Tissues
We will continue our discussion of the Squid and Vibrio symbiosis as it relates to tissue
remodeling. An important mechanism for host remodeling of tissues is the evolutionarily
conserved process of apoptosis, which is also key to the modeling of tissues during embryo
development. We will examine the genetic and cell biological strategies for characterizing the
mechanism by which bacterial signals induce localized cellular apoptosis.

Cloud-Hansen (2006) Breaching the great wall: peptidoglycan and microbial interactions.
Nat Rev Microbiol 4(9):710-6.
6



Koropatnick (2004) Microbial factor-mediated development in a host-bacterial
mutualism. Science 306(5699):1186-8.
Troll (2009) Peptidoglycan induces loss of a nuclear peptidoglycan recognition protein
during host tissue development in a beneficial animal-bacterial symbiosis. Cell Microbiol
11(7):1114-27.
Chun (2008) Effects of colonization, luminescence, and autoinducer on host transcription
during development of the squid-vibrio association. PNAS 105(32):11323-8.
Week 10. Host Manipulation in Pathogenesis
We will shift our focus from beneficial host-microbe interactions to those detrimental
interactions in which bacteria cause disease and tissue damage within the host. It is becoming
increasingly clear that harmful bacteria use many of the same tools as beneficial bacteria in
manipulating their host. We will examine how pathogenic bacteria manipulate essential aspects
of host physiology in order to promote disease, and contrast this with what we have previously
learned about beneficial interactions.





Walker (2008) Emerging and re-emerging rickettsioses: endothelial cell infection and
early disease events. Nat Rev Microbiol 6(5):375-86.
Martinez (2004) Early signaling events involved in the entry of Rickettsia conorii into
mammalian cells. J Cell Sci 117(Pt 21):5097-106.
Chan (2009) Rickettsial outer-membrane protein B (rOmpB) mediates bacterial invasion
through Ku70 in an actin, c-Cbl, clathrin and caveolin 2-dependent manner. Cell
Microbiol 11(4):629-44.
Coburn (2007) Type III secretion systems and disease. Clin Microbiol Rev 20(4):535-49.
Alto (2006) Identification of a bacterial type III effector family with G protein mimicry
functions. Cell 124(1):133-45.
Week 11. Host Defense Responses
Innate immunity represents the first line of defense against pathogens in all plants and animals.
However, a host must first be able to detect the presence of a pathogen within its tissues. We will
examine several methods for identifying host genes involved in detecting and combating
bacterial infection. We will then discuss the function of several genes induced by innate immune
pathways that contribute to antibacterial immunity.




Ausubel (2005) Are innate immune signaling pathways in plants and animals conserved?
Nat Immunol 6(10):973-9.
Ronald (2010) Plant and animal sensors of conserved microbial signatures. Science
330(6007):1061-4.
Arbibe (2007) An injected bacterial effector targets chromatin access for transcription
factor NF-kappaB to alter transcription of host genes involved in immune responses. Nat
Immunol 8(1):47-56.
Asai (2002) MAP kinase signalling cascade in Arabidopsis innate immunity. Nature
415(6875):977-83.
7

Stockhammer (2009) Transcriptome profiling and functional analyses of the zebrafish
embryonic innate immune response to Salmonella infection. J Immunol 182(9):5641-53.
Week 12. Evolutionary Origin of Pathogens
The evolution of bacteria is associated with continuous generation of novel genetic variants. The
major driving forces in this process are point mutations, genetic rearrangements, and importantly
horizontal gene transfer. A large number of human and animal bacterial pathogens have evolved
the capacity to produce virulence factors that are directly involved in infection and antibiotic
resistance. Because these factors are often located on mobile DNA elements, they can be
transferred between bacteria. We will discuss the role of horizontal gene transfer in the evolution
and acquisition of virulence traits.



Ziebuhr (1999) Evolution of bacterial pathogenesis. Cell Mol Life Sci 56(9-10):719-28.
Batut (2004) The evolution of chronic infection strategies in the alpha-proteobacteria. Nat
Rev Microbiol 2(12):933-45.
Nakagawa (2007) Deep-sea vent epsilon-proteobacterial genomes provide insights into
emergence of pathogens. PNAS 104(29):12146-50.
WEEK 13. Mammalian gut microbiome.
Humans are metagenomic in that we are a composite of both our genes and those of all our
associated microbes. The bacteria that make up the human gut microbiome form an essential
organ that helps digest food and provides vitamins, regulates gut development in infants, and
promotes development of the innate immune response. We will examine methods for identifying
and categorizing the diverse bacterial species that make up the human gut microbiome, as well as
benefits of this bacterial community to human health.





Ley (2008) Evolution of mammals and their gut microbes. Science 320(5883):1647-51.
Eckburg (2005) Diversity of the human intestinal microbial flora. Science
308(5728):1635-8.
Macpherson (2004) Interactions between commensal intestinal bacteria and the immune
system. Nat Rev Immunol 4(6):478-85.
Mazmanian (2005) An immunomodulatory molecule of symbiotic bacteria directs
maturation of the host immune system. Cell 122(1):107-18.
Mazmanian (2008) A microbial symbiosis factor prevents intestinal inflammatory
disease. Nature 453(7195):620-5.
Week 14. Mammalian gut microbiome.
Unlike pathogens that cause disease during short-term infections, the bacteria that make up the
human microbiome establish a lifelong cohabitation within their host. However, very little is
known regarding the molecular mechanisms that promote long-term colonization and this
remains at the forefront of gut microbiome research. We will learn about one gut bacterium that
has been examined and the important role that bacterial cell surface polysaccharides play in
promoting stable, long-term gut colonization.
8




Rakoff-Nahoum (2004) Recognition of commensal microflora by toll-like receptors is
required for intestinal homeostasis. Cell 118(2):229-41.
Dethlefsen (2007) An ecological and evolutionary perspective on human-microbe
mutualism and disease. Nature 449(7164):811-8.
Liu (2008) Regulation of surface architecture by symbiotic bacteria mediates host
colonization. PNAS 105(10):3951-6.
Blaser (2007) The equilibria that allow bacterial persistence in human hosts. Nature
449(7164):843-9.
9